tbuckley/cabot-search huggingface dataset:
NIMG-86. ESTIMATING BRAIN TUMOR RELATED EDEMA FROM NON-INVASIVE IMAGING IN A CLINICALLY RELEVANT TIMELINE
Authors: Pamela Jackson, Sara Ranjbar, Kyle Singleton, Kristin Swanson
Journal: Neuro-Oncology (2023)

Abstract Image-based mathematical modeling is emerging as an advantageous tool to integrate into the care routine for patients with brain tumors. These tools can be used for a variety of tasks including predicting tumor growth, indicating spatial genomic alterations, and guiding radiation therapy. Often, the methods to produce these maps are developed in silos, using cohorts of retrospective patients and switching to a per patient map calculation can be an afterthought. Automatic pipelines are needed to enable creating mathematical maps in a clinically-relevant workflow. To this end, we developed a pipeline to create an image-based mathematical map of edema abundance based on T2-weighted (T2W) magnetic resonance imaging that includes preprocessing steps, abnormality and tissue type segmentation, brain extraction, map generation, and conversion between image file formats. The python-based pipeline was designed to take in T1-weighted (T1W), T1W with gadolinium contrast (T1Gd), T2W, and fluid attenuated inversion recovery (FLAIR) DICOM images for a single patient as input and convert them to NIfTIs for downstream steps. The pipeline preprocessed images by correcting bias field fluctuations using the N4 algorithm and normalizing intensities. The T1W, T1Gd, and FLAIR are then registered to the T2W. T1Gd and FLAIR are used in a deep learning algorithm to delineate the brain and abnormality including enhancing tumor, necrosis, and peripheral edema. Normal tissue segmentations are performed using the statistical parametric mapping (SPM) segmentation routine. The segmentations and preprocessed images are all utilized in the edema mathematical model. The resulting edema map is then reformatted as a DICOM and output for further use by clinicians and clinical imaging systems. Our future goals include integrating our pipeline in a clinical workstation and sending final maps to our hospital’s picture archiving and communication system (PACS) to allow for deployment of these models for patient care in a clinically efficient timeline.
EPID-29. ASSOCIATIONS BETWEEN PM2.5, VEGETATION DENSITY AND CHILDHOOD BRAIN TUMORS: A CASE-CONTROL REGISTRY-BASED STUDY FROM TEXAS 1995-2011
Authors: Lindsay Williams, David Haynes, Jeannette Sample, Ali Hossaini, Laura McGuinn, Thanh Hoang, Philip Lupo, Michael Scheurer
Journal: Neuro-Oncology (2023)

Abstract BACKGROUND Air pollution has been reported to be associated with childhood leukemia, and increasing vegetation density (greenness) has been inversely associated with adult cancer incidence. However, the interplay between air pollution and greenness in childhood brain tumor (CBT) etiology is unclear. We sought to estimate the association between prenatal exposure to air pollution, greenness, and CBTs in Texas (1995-2011). Materials and METHODS We included 1,316 individuals with a CBT diagnosed ≤ 16 years of age and 109,762 age- and sex-matched controls. We linked birth certificate residential address to census tract annual average particulate matter 2.5 µg/m³ (PM2.5) and Normalized Difference Vegetation Index (NDVI) to approximate prenatal exposure to air pollution and greenness. We estimated odds ratios (OR) and 95% confidence intervals (95% CI) between CBTs, PM2.5 and NDVI interquartile range (IQR) increases. Models were adjusted for birth year, sex, race/ethnicity, and area-level socioeconomic status. RESULTS Ependymoma (n=136), astrocytoma (n=619), medulloblastoma (n=187), PNET (n=57), ATRT (n=54), and other gliomas (n=263) were included. Average birth year PM2.5 and NDVI exposure levels were similar in cases and controls, 11 µg/m³ and 0.4, respectively. Each IQR increase (2.6µg/m³) in PM2.5 was associated with ependymoma (OR: 1.27, 95% CI: 1.01-1.60), adjusting for NDVI. After adjusting for PM2.5 quartiles, each IQR increase in NDVI (0.13) was inversely associated with ependymoma in those diagnosed at 0-4 years of age (OR: 0.75, 95% CI: 0.56-0.97) and medulloblastoma in those aged 0-16 years at diagnosis (OR: 0.75, 95% CI: 0.62-0.91). There was no evidence of statistical interaction for any CBT. CONCLUSIONS Increasing air pollution during the prenatal period increased risk of childhood ependymoma, independent of greenness. Conversely, increasing greenness prenatal exposure decreased the risk of ependymoma and medulloblastoma, independent of PM2.5. These findings highlight the complex relationship between air pollution and greenness in CBT etiology.
QOL-11. ADAPTING CALM PSYCHOTHERAPY FOR CAREGIVERS OF PATIENTS WITH MALIGNANT GLIOMA
Authors: Kelcie Willis, Amber Fox, Morgan Reid, Lillia Thumma, Sarah Barrett, Karen Lo, Ashlee Loughan
Journal: Neuro-Oncology (2023)

Abstract Caregivers of patients with malignant gliomas (PwMG) report significant emotional distress yet are often omitted from supportive psycho-oncology programs. CALM (Managing Cancer and Living Meaningfully), an evidence-based psychotherapy, has shown preliminarily to reduce depressive and existential distress among PwMG. While caregivers are invited to participate in CALM alongside the patient, the benefit of CALM for caregivers has not yet been evaluated. This NIH ORBIT model phase 1a qualitative study sought to assess caregivers’ interest in CALM and their recommendations to adapt the intervention to their emotional needs. Bereaved caregivers (N = 22, Mage = 47.2, 77% female, 73% White) of PwMG participated in 90-minute focus groups (n = 4-7). Caregivers first received psycho-education on CALM and then participated in a semi-structured group interview. Sessions were audio-recorded, transcribed, and coded by five independent coders using thematic content analysis and NVivo software (kappa = .80-.94). Three major themes were explored: 1) CALM’s relevancy to the neuro-oncology caregiving experience; 2) the suitability of CALM for PwMG caregivers; and 3) suggested adaptations to CALM for PwMG caregivers. First, caregivers felt the four domains of CALM mirrored their experience of caregiving. Secondly, they noted both strengths and weaknesses of the intervention. Lastly, caregivers provided valuable recommendations to improve the timing (e.g., introduce CALM early, continuously), content (e.g., include sessions about bereavement and caregiver burden), and format (e.g., both independent and joint sessions) of the CALM intervention. Examples of each theme will be provided. The results suggest that CALM may be a potentially impactful intervention for the emotional needs of caregivers of PwMG. Nevertheless, adjustments to the timing, content, and format of this intervention are warranted, prior to a future feasibility/acceptability trial. This study not only provides the foundational data required to proceed with future CALM trials, but it also provides valuable considerations for those developing interventions for caregivers of PwMG largely.
DDEL-08. THE OMMAYA IN LEPTOMENINGEAL DISEASE AND CENTRAL NERVOUS SYSTEM MALIGNANCIES: A RESERVOIR OF THE PAST OR SOURCE OF THE FUTURE?
Authors: Eris Spirollari, Sima Vazquez, Daniel Durkin, Jacob Fliegelman, Austin Carpenter, Jose Dominguez, Simon Hanft
Journal: Neuro-Oncology (2023)

Abstract Advances in systemic therapies have increased survival in patients with metastatic cancer. However, such prolonged survival has been associated with increased incidence of leptomeningeal disease (LMD), a late-stage manifestation of cancer to the leptomeninges that carries a dismal prognosis. Circumvention of the blood-brain-barrier to treat LMD can be accomplished with intraventricular therapy using an Ommaya reservoir. Our objective is to determine the indications, efficacy, and future directions of the Ommaya reservoir in LMD and CNS malignancies. A systematic review of the literature was conducted. Data extracted from articles included year of publication, study design, cancer types, and findings. The search query returned 5,338 articles, of which 94 were included. Most articles (45, 47.9%) were prospective cohort studies. Forty-one (43.6%) described retrospective chart reviews, and five (5.3%) described RCTs. Ommaya was studied as a vehicle for intrathecal chemotherapy administration (76, 80.9%), an access site for CSF sampling (12, 12.8%), or a device through which to study dosimetry and pharmacokinetics of various drugs (5, 5.3%). Most studies (50, 53.2%) explored the use of Ommaya in LMD, secondary to any cancer (62%), breast cancer (20%), lung cancer (6%), glioma (6%), lymphoma (4%), and melanoma (2%). Sixteen articles (17%) focused on the use of Ommaya in malignant glioma, 11 studies (11.7%) in CNS lymphoma, and three (3, 3.2%) evaluated the efficacy of intraventricular morphine for intractable cancer pain. Since 2011, 24 studies (64.9%) reported positive outcomes with Ommaya, and two (5.4%) did not. The literature indicates that the Ommaya is a safe and reliable option for treatment of certain malignancies and LMD. The benefit appears to be most marked in the era of multi-modality treatment for cancer, particularly breast. Most recently, and perhaps most promising, is utilization of Ommaya for CSF analysis, both in tracking therapeutic response and defining pharmacokinetics in patients with LMD.
NCOG-26. CORE OUTCOME SETS FOR USE IN FUTURE MENINGIOMA CLINICAL STUDIES: RESULTS OF THE COSMIC PROJECT
Authors: Christopher Millward, Abdurrahman Islim, Sumirat Keshwara, Nisaharan Srikandarajah, Andrew Brodbelt, Anthony Marson, Paula Williamson, Michael Jenkinson
Journal: Neuro-Oncology (2023)

Abstract OBJECTIVE Core Outcome Sets (COS) define the minimum outcomes that should be measured and reported in all clinical trials for a specific health condition or health area. The aim was to develop two COS for intracranial meningioma; one for clinical trials (COSMIC: Intervention) and one for observational studies (COSMIC: Observation). METHODS A study advisory group was formed with representation from international stakeholders of charities (IBTA, TBTC, brainstust), neurosurgery societies (SBNS, BIMS) and neuro-oncology societies (BNOS, EANO, EORTC, ICOM, RANO-PRO, SNO). Two systematic literature reviews and trial registry searches were performed to identify outcomes reported in published and ongoing 1) meningioma clinical trials, and 2) studies of incidental/untreated meningioma. Outcomes were deduplicated and categorised. Individuals were recruited from stakeholder groups (including meningioma patients and carers, healthcare professionals, researchers) to participate in 2-round, international, modified eDelphi surveys. The final core outcome sets were ratified through online consensus meetings. RESULTS The COSMIC: Intervention systematic review identified 660 verbatim outcomes, rationalized into 24 Delphi survey items. Following the consensus meeting, 15 outcomes were included in the final set. For COSMIC: Observation, 267 verbatim outcomes were identified and rationalized into 17 Delphi survey items. 16 outcomes were included in the final set. There were eight core outcomes common to both COSMIC: Intervention and COSMIC: Observation COS, namely tumour growth, physical, emotional, and neurocognitive functioning, overall quality of life, progression-free survival, meningioma specific mortality and overall survival. Role and social functioning were core outcomes in COSMIC Observation but not COSMIC intervention. CONCLUSIONS The COSMIC study has defined the core outcome sets for use in future meningioma clinical trials and studies. Role and social functioning were important to incidental meningioma patients and likely reflects the anxiety and uncertainty around clinical treatment. International stakeholder agreement should ensure widespread use and adoption.
CTNI-69. REAL-TIME DRUG SCREENING AND GENOMIC TESTING TO DETERMINE INDIVIDUALIZED TREATMENT PLANS IN CHILDREN AND YOUNG ADULTS WITH RELAPSED MEDULLOBLASTOMA: PRELIMINARY REPORT OF PNOC027
Authors: Margaret Shatara, Megan R Paul, Janel Boyle-Lang, Ashley Meyer, Shannon Raber, Lanipua Yeh-Nayre, Aimee Jalkanen, Lindsay Kilburn, Roger Packer, Jennifer Elster, Alyssa T Reddy, Carl Koschmann, Adam Kraya, Adam Resnick, Michael Prados, Cassie Kline, Sabine Mueller, Robert J Wechsler-Reya, Joshua B Rubin
Journal: Neuro-Oncology (2023)

Abstract While current upfront multi-modal treatment for medulloblastoma is effective in many cases, for patients who relapse or don’t respond to initial therapy, effective treatment options are limited and novel therapeutic approaches are needed. The Pacific Pediatric Neuro-Oncology Consortium (PNOC) PNOC027 clinical trial investigates a precision medicine approach that combines real-time drug screening with whole exome and RNA sequencing of fresh tumor tissue to inform individualized treatment recommendations for children and young adults with relapsed medulloblastoma. The primary endpoint is to determine the feasibility of incorporating real time drug screening with DNA/RNA sequencing of tumor to develop a treatment regimen of up to 4-drug of FDA approved agents within 21 business days of tumor acquisition. To this end, freshly isolated cells from relapsed medulloblastoma tumor tissue undergo high-throughput drug screening using a platform of 232 clinically available compounds in parallel with multi-omic genomic analyses to predict individualized tumor response to treatment. Drug responses are assessed after 72 hours of drug exposure and the results yield drug prioritizations based on cytotoxicity and predicted blood-brain barrier permeability. Drugs from different classes are selected based on results from drug screening and molecular analyses combined with patient age, prior treatments, and other medical conditions. Four patients have been enrolled to date and viable tissue samples have been successfully collected and analyzed with treatment recommendations rendered within 21 business days for all patients. The five drug classes with the highest in vitro responses on the drug screen are HDAC inhibitors, proteosome inhibitors, anthracyclines, DNA crosslinkers and kinase inhibitors. PNOC027 demonstrates preliminary feasibility of real-time drug screening combined with DNA/RNA sequencing to inform targeted therapy selection for patients with relapsed medulloblastoma in clinically relevant timeframes. The trial is informing an expanded precision-based approach for relapsed medulloblastoma and the impact of genetic and epigenetic alterations on treatment response.
DDEL-11. FOCUSED ULTRASOUND-MEDIATED DELIVERY OF ANTI-PROGRAMMED CELL DEATH-LIGAND 1 ANTIBODY TO THE BRAIN OF A PORCINE MODEL
Authors: Siaka Fadera, Chinwendu Chukwu, Andrew H Stark, Yimei Yue, Jinyun Yuan, Chih-Yen Chien, Lu Xu, Mohammad Albuhssin, Hong Chen
Journal: Neuro-Oncology (2023)

Abstract Focused ultrasound-combined with microbubble-mediated blood-brain barrier opening (FUS-BBBO) has been established as a promising brain drug delivery technology for the treatment of brain tumors. Immune checkpoint inhibitor therapy is a form of cancer immunotherapy that has revolutionized the treatment of cancer and shown remarkable efficacy in a range of cancers. Previous studies reported successful delivery of a checkpoint inhibitor anti-PD-L1 antibody (aPD-L1) by FUS-BBBO in the mouse brain. The objective of this study was to evaluate the feasibility and safety of FUS-BBBO in the delivery of aDP-L1 to the brain of a large animal model. Pigs (4 weeks old, male, n=3) were used as the large animal model. A FUS transducer (frequency of 650 kHz, aperture of 65 mm, and a focal length of 65 mm) was used to sonicate three different brain regions in the presence of systemically injected microbubbles (Definity) for every pig. Near-infrared fluorescent dye-labeled aPD-L1 was injected intravenously to the pig after FUS sonication. Contrast-enhanced MRI was conducted to evaluate the BBB permeability. Pig brains were then harvested and imaged by the Licor Pear imaging system. Successful BBBO was confirmed by in vivo T1-weighted MR imaging. The average MR contrast enhancement volume in the FUS-targeted regions was 4.8× of that in the contralateral non-targeted regions. Ex vivo fluorescence imaging found that FUS sonication enhanced aPD-L1 delivery by 2.1× compared with the non-targeted regions. Histological analysis by hematoxylin and eosin (H&amp;E) staining did not find evidence for tissue damage. These findings suggest that FUS-BBBO can achieve noninvasive, localized, and safe delivery of aPD-L1 to the brain of large animals, providing strong preclinical data to support the clinical translation of this promising technique for brain cancer immunotherapy.
TMET-22. MULTI-OMIC SCREENING OF INVASIVE GBM CELLS IN ENGINEERED BIOMATERIALS AND PATIENT BIOPSIES REVEALS TARGETABLE TRANSSULFURATION PATHWAY ALTERATIONS
Authors: Nikita Choudhary, Joseph Garcia, Erin Akins, Saket Jain, Kayla Wolf, Jason Zhang, Meeki Lad, Poojan Shukla, Sabraj Gill, Will Carson, Luis Carrete, Allison Zheng, Sanjay Kumar, Manish Aghi
Journal: Neuro-Oncology (2023)

Abstract While the poor prognosis of glioblastoma arises from the invasion of a subset of tumor cells, little is known of the metabolic alterations within these cells that fuel invasion. We integrated spatially addressable hydrogel biomaterial platforms, patient site-directed biopsies, and multi-omics analyses to define metabolic drivers of invasive glioblastoma cells. Metabolomics and lipidomics revealed elevations in the redox buffers cystathionine, hexosylceramides, and glucosyl ceramides in the invasive front of both hydrogel-cultured tumors and patient site-directed biopsies, with immunofluorescence indicating elevated reactive oxygen species (ROS) markers in invasive cells. Transcriptomics confirmed upregulation of ROS-producing and response genes at the invasive front in both hydrogel models and patient tumors. Amongst oncologic ROS, hydrogen peroxide specifically promoted glioblastoma invasion in 3D hydrogel spheroid cultures. A CRISPR metabolic gene screen revealed cystathionine gamma lyase (CTH), which converts cystathionine to the non-essential amino acid cysteine in the transsulfuration pathway, to be essential for glioblastoma invasion. Correspondingly, supplementing CTH knockdown cells with exogenous cysteine rescued invasion. Pharmacologic CTH inhibition suppressed glioblastoma invasion, while CTH knockdown slowed glioblastoma invasion in vivo. Our studies highlight the importance of ROS metabolism in invasive glioblastoma cells and support further exploration of the transsulfuration pathway as a mechanistic and therapeutic target.
NIMG-27. GLIOBLASTOMA IN THE MAKING? ADVANCED IMAGING TELLS "MOLECULAR GLIOBLASTOMA" APART FROM ASTROCYTOMA
Authors: Michael Griessmair, Marie-Christin Metz, Claus Zimmer, Benedikt Wiestler
Journal: Neuro-Oncology (2023)

Abstract The fifth WHO classification of tumors of the CNS allows the diagnosis of glioblastoma using specific molecular markers, even if the classical histological criteria (necrosis and neoangiogenesis) are not fulfilled. Since such cases also tend to lack blood-brain barrier disruption and necrosis on conventional imaging, these can be mistaken for low-grade astrocytomas. We investigated the potential of advanced imaging to capture tumor biology and thus reliably distinguish between those entities already preoperatively. Multimodal preoperative 3T-MRI scans were collected from 147 glioblastoma, 4 astrocytomas grade 4, 7 “Molecular glioblastoma” (molGBM) grade 4, 9 astrocytomas grade 2, and 12 astrocytomas grade 3. From AI-based multi-compartimental tumor segmentations, advanced imaging metrics from perfusion- and diffusion-imaging were automatically extracted. Two-sample t-test and one-way ANOVA analysis was performed to test for significant differences between apparent diffusion coefficient (ADC) and relative cerebral blood volume (rCBV). Interestingly, rCBV (signifying neoangiogenesis) was significantly higher in molGBM as opposed to astrocytomas for the 5th percentile as well as for mean and median values (p &amp;lt; 0.05). ADC values were consequently lower (indicating higher cellularity) in molGBM than in astrocytomas grade 2 and 3 in the 95th percentile (p &amp;lt; 0.05). Although no molGBM showed contrast-enhancement initially, one untreated case showed a flaccid barrier disruption at 30d follow-up. Interestingly, the molecular imaging at the earlier timepoint showed significantly higher CBV values in the non-enhancing tumor than common glioblastoma and astrocytoma grade 4 (p = 0.013, ANOVA), which indicates highly active tumor portions. Perhaps it is precisely these areas that are on the verge of barrier disruption. Our results support the hypothesis that molGBM are truly early glioblastomas. Better understanding the molecular mechanisms involved in the transition to “classical” glioblastoma promises to provide important insight into tumor biology and potential therapeutic targets.
EOLP-02. EFFECT OF HEALTH DISPARITIES ON END OF LIFE CARE IN GLIOBLASTOMA, IDH WILDTYPE (GBM) PATIENTS
Authors: Cassandra Helfer, Ethan Ludmir, Paige Farinholt, Ganesh Rao, Akash Patel, Ali Jalali, Jacob Mandel
Journal: Neuro-Oncology (2023)

Abstract GBM is the most common malignant brain tumor in adults. Given the highly aggressive course and rapid neurologic decline, end of life care is critical. Proactive referral to hospice care is associated with improved quality of life and is recommended under current oncology guidelines. Utilization of these services is limited, with hospice referral rates ranging from 60-75%. The role of healthcare disparities upon quality of end of life care remains unclear. The goal of this study was to investigate the influence of healthcare disparities upon hospice service utilization by comparing patients at Ben Taub (BT), a Houston public safety net hospital, to Baylor St. Luke’s (BSL), a private academic institution. 50 patients (16 BT, 34 BSL) diagnosed with GBM, IDH wildtype, since 2016 were analyzed via retrospective chart review. Patient demographics and insurance status varied, with BT patients more likely to be Hispanic or African American (BT 94%, BSL 29%) and to be uninsured or insured via the county financial aid program (BT 88%, BSL 6%). Hospice referral rates were overall consistent with prior studies (BT 75%, BSL 68%). BT patients were referred to hospice later (BT 3.8, BSL 5.5 weeks mean survival after referral, p=0.118) and were more likely to be referred while in an inpatient setting (BT 75%, BSL 36%, p=0.07). Additionally, BT patients were more likely to be admitted to the hospital in the month prior to death (BT 44%, BSL 33%, p=0.537) and to die in an inpatient setting (BT 19%, BSL 3%, p=0.096). These findings call attention to the impact of healthcare disparities upon utilization of end of life services. Further research is needed to investigate factors contributing to these discrepancies and implement tools to improve quality of life in all patients with late-stage GBM regardless of race, socioeconomic, or insurance status.